Brief description of study

This randomized phase III trial studies axillary lymph node dissection to see how well it
works compared to axillary radiation therapy in treating patients with node-positive breast
cancer treated with neoadjuvant chemotherapy followed by surgery. Lymph node dissection may
remove cancer cells that have spread to nearby lymph nodes in patients with breast cancer.
Radiation therapy uses high-energy x-rays to kill tumor cells. This study will evaluate
whether radiation therapy is as effective as lymph node dissection.

Detailed Study Description

Study Outline:

All patients will undergo surgery to identify sentinel lymph node(s). If a lymph node
(sentinel or non-sentinel) is determined to be positive on intra-operative pathology the
patient will be registered/randomized intra-operatively.

Patients who do not have a sentinel lymph node identified will not be
registered/randomized to the study.

Patients whose sentinel lymph node status is cannot be/is not determined intraoperatively,
and have not undergone ALND, but had at least one lymph node (sentinel or
non-sentinel) found to be positive on final pathology review will be
registered/randomized post-operatively.

Patients whose sentinel lymph node status is found to be negative intra-operatively and
have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel)
found to be positive on final pathology review will be registered/randomized
post-operatively.

ALND is not to be performed prior to registration/randomization.

Patients who are determined to have negative lymph nodes on final pathology will not be
registered/randomized, but can be offered participation in another cooperative group
trial.

The primary and secondary objectives of the study are described below. Please see the "Arms"
section for a detailed description of the treatment regimens.

Primary Objective:

To evaluate whether radiation to the undissected axilla and regional lymph nodes is not
inferior to axillary lymph node dissection with radiation to the regional lymph nodes
but not to the dissected axilla in terms of invasive breast cancer recurrence-free
interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy

Secondary Objectives:

To evaluate whether radiation to the undissected axilla and regional lymph nodes is not
inferior to axillary lymph node dissection with radiation to the regional lymph nodes
but not to the dissected axilla in terms of the incidence of invasive loco-regional
recurrences in patients with a positive SLN(s) after completion of neoadjuvant
chemotherapy

To obtain an estimate of the distribution of residual disease burden scores for each
treatment arm

To estimate the distribution of overall survival for each treatment arm

Patients may receive adjuvant and ancillary therapy as appropriate per the protocol.

Adjuvant Therapy:

Adjuvant endocrine therapy: Patients with hormone receptor (ER and/or PR) positive
disease should receive a minimum of 5 years of standard endocrine therapy (experimental
agents/regimens are not permitted). Endocrine therapy should begin following completion
of neoadjuvant chemotherapy and surgery, either before, during or after radiation
therapy at the discretion of the oncologist. Selection of the agents is at the treating
physician's discretion.

Patients with HER 2 positive disease should complete a total of one year of trastuzumab
therapy (over the neoadjuvant and adjuvant period).

Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not
allowed.

Patients who wish to receive any of these therapies after surgery must go off study at the
time of their initiation.

Ancillary Therapy:

Patients should receive full supportive care, including transfusions of blood and blood
products, erythropoetin (unless otherwise specified in the protocol), antibiotics,
antiemetics, etc. when appropriate.

Patients are followed up for 5 years after completion of radiation therapy.